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Nanowire transistor arrays for mapping neural circuits in acute brain slices.

ABSTRACT: Revealing the functional connectivity in natural neuronal networks is central to understanding circuits in the brain. Here, we show that silicon nanowire field-effect transistor (Si NWFET) arrays fabricated on transparent substrates can be reliably interfaced to acute brain slices. NWFET arrays were readily designed to record across a wide range of length scales, while the transparent device chips enabled imaging of individual cell bodies and identification of areas of healthy neurons at both upper and lower tissue surfaces. Simultaneous NWFET and patch clamp studies enabled unambiguous identification of action potential signals, with additional features detected at earlier times by the nanodevices. NWFET recording at different positions in the absence and presence of synaptic and ion-channel blockers enabled assignment of these features to presynaptic firing and postsynaptic depolarization from regions either close to somata or abundant in dendritic projections. In all cases, the NWFET signal amplitudes were from 0.3-3 mV. In contrast to conventional multielectrode array measurements, the small active surface of the NWFET devices, approximately 0.06 microm(2), provides highly localized multiplexed measurements of neuronal activities with demonstrated sub-millisecond temporal resolution and, significantly, better than 30 microm spatial resolution. In addition, multiplexed mapping with 2D NWFET arrays revealed spatially heterogeneous functional connectivity in the olfactory cortex with a resolution surpassing substantially previous electrical recording techniques. Our demonstration of simultaneous high temporal and spatial resolution recording, as well as mapping of functional connectivity, suggest that NWFETs can become a powerful platform for studying neural circuits in the brain.

SUBMITTER: Qing Q

PROVIDER: S-EPMC2808222 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Extracellular recordings by means of high-density microelectrode arrays (HD-MEAs) have become a powerful tool to resolve subcellular details of single neurons in active networks grown from dissociated cells. To extend the application of this technology to slice preparations, we developed models describing how extracellular signals, produced by neuronal cells in slices, are detected by microelectrode arrays. The models help to analyze and understand the electrical-potential landscape in an in vitro HD-MEA-recording scenario based on point-current sources. We employed two modeling schemes, (i) a simple analytical approach, based on the method of images (MoI), and (ii) an approach, based on finite-element methods (FEM). We compared and validated the models with large-scale, high-spatiotemporal-resolution recordings of slice preparations by means of HD-MEAs. We then developed a model-based localization algorithm and compared the performance of MoI and FEM models. Both models provided accurate localization results and a comparable and negligible systematic error, when the point source was in saline, a condition similar to cell-culture experiments. Moreover, the relative random error in the x-y-z-localization amounted only up to 4.3% for z-distances up to 200 μm from the HD-MEA surface. In tissue, the systematic errors of both, MoI and FEM models were significantly higher, and a pre-calibration was required. Nevertheless, the FEM values proved to be closer to the tissue experimental results, yielding 5.2 μm systematic mean error, compared to 22.0 μm obtained with MoI. These results suggest that the medium volume or "saline height", the brain slice thickness and anisotropy, and the location of the reference electrode, which were included in the FEM model, considerably affect the extracellular signal and localization performance, when the signal source is at larger distance to the array. After pre-calibration, the relative random error of the z-localization in tissue was only 3% for z-distances up to 200 μm. We then applied the model and related detailed understanding of extracellular recordings to achieve an electrically-guided navigation of a stimulating micropipette, solely based on the measured HD-MEA signals, and managed to target spontaneously active neurons in an acute brain slice for electroporation.

Project description:The well-established planar multi-electrode array recording technique was used to investigate neural circuits and temporal plasticity in the hindlimb representation of the rat primary somatosensory cortex (S1 area).Freshly dissociated acute brain slices of rats were subject to constant perfusion with oxygenated artificial cerebrospinal fluid (95% O(2) and 5% CO(2)), and were mounted on a Med64 probe (64 electrodes, 8x8 array) for simultaneous multi-site electrophysiological recordings. Current sources and sinks across all the 64 electrodes were transformed into two-dimensional current source density images by bilinear interpolation at each point of the 64 electrodes.The local intracortical connection, which is involved in mediation of downward information flow across layers II-VI, was identified by electrical stimulation (ES) at layers II-III. The thalamocortical connection, which is mainly involved in mediation of upward information flow across layers II-IV, was also characterized by ES at layer IV. The thalamocortical afferent projections were likely to make more synaptic contacts with S1 neurons than the intracortical connections did. Moreover, the S1 area was shown to be more easily activated and more intensively innervated by the thalamocortical afferent projections than by the intracortical connections. Finally, bursting conditioning stimulus (CS) applied within layer IV of the S1 area could successfully induce long-term potentiation (LTP) in 5 of the 6 slices (83.3%), while the same CS application at layers II-III induced no LTP in any of the 6 tested slices.The rat hindlimb representation of S1 area is likely to have at least 2 patterns of neural circuits on brain slices: one is the intracortical circuit (ICC) formed by interlaminar connections from layers II-III, and the other is the thalamocortical circuit (TCC) mediated by afferent connections from layer IV. Besides, ICC of the S1 area is spatially limited, with less plasticity, while TCC is spatially extensive and exhibits a better plasticity in response to somatosensory afferent stimulation. The present data provide a useful experimental model for further studying microcircuit properties in S1 cortex at the network level in vitro.

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Nanowire transistor arrays for mapping neural circuits in acute brain slices.

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